Role of Plant Flavonoids In Mammalian

Cell Inflammation
Dr.Dahiphale Hanumant Venkatrao
DEPARTMENT OF VETERINARY PHARMACOLOGY AND TOXICOLOGY
COVAS, PARBHANI

Flavonoids (or bioflavonoids)

1) From the Latin word flavus meaning yellow
color in nature
2) Are a class of plant secondary metabolites.
3) Flavonoids were referred to as Vitamin P .

Flavonoids:
source
Dietary
sources
Fruit and vegetables:
(All classes)
Tea:
(Flavanols)

Citrus:
(Flavanone)

Red wine:
(Flavanol, Flavonols)

Cocoa:
(Flavanols
and procyanidins)

Berries:
(Anthocyanins)

Seperation techniques
1)
2)
3)
4)

Thin layer chromatography (TLC)

High Performance Liquid Chromatography
Paper Chromatography
Column Chromatography

structures

1) These are low molecular weight substances.

2) Are phenylbenzo- pyrones.
3) Structures are based on a common threering nucleus.

Flavonoids: structure
R1
R1

R2
HO

O
R3

R3

R1

OH

R2

OH

OH
HO

Flavanol

R4
R5

Isoflavone

R2
OH

OH
Anthocyanin

R1

R1
R2

R2
HO

R3

HO

OH
OH

O
Flavonol

OH

O
Flavanone

R3

Proposed mechanisms underlying the inflammatory

effects of flavonoids
1) Antioxidative activities

2)
Modulation of
inflammatory related
cell functions

3)
Modulation of
proinflammatory
enzyme activities

4)
Modulation of the
production of other
proinflammatory molecules

5)
Modulation of
proinflammatory
gene expression

Proposed mechanisms underlying the

inflammatory effects of flavonoids
Several mechanisms explaining the anti-inflammatory
activity of flavonoids have been described, including
1) Antioxidative
activities
2) Modulation of
inflammatory related
cell functions

3) Modulation of
proinflammatory
enzyme activities

4) Modulation of the
production of other
proinflammatory molecules

5) Modulation of
proinflammatory
gene expression

Antioxidative activities
ACTIVITY

MECHANISM

EFFECT

Radical
scavanging
Antioxidative
activities

Inhibition of
ROS
production
Inhibition of
pro-oxidant
enzyme

Free radical
Lipid
peroxidation

1) Body cells and tissues are continuously threatened by the

damage caused by free radicals and reactive oxygen

species.
2) which are produced during normal oxygen metabolism.
3) The increased production of reactive oxygen species leads
to forms of tissue injury.
4) which have been implicated in a multitude of disease
states ranging from inflammatory injury to myocardial
infarction and cancer.

5) The mechanisms and the sequence of events by which free

radicals interfere with cellular functions are not fully
understood
6) But some of the detrimental effects in biological systems
includes.
a) Peroxidation of membrane lipids,
b) Oxidative damage to nucleic acids or
carbohydrates and
c) The oxidation of sulfhydryl and other susceptible
groups in proteins.
7) In addition, free radicals can attract various inflammatory
mediators contributing to a generalized inflammatory
response and tissue damage

flavonoids are powerful in vitro antioxidants, being

able to scavenge a wide range of free radicals, as well as to
inhibit their formation.

Modulation of inflammatory
related cell functions
ACTIVITY

Modulation of
inflammatory
related
cell functions

MECHANISM

EFFECT

Modulation
of enzymatic
activity
Inflammatory
cells activation
Modulation of
Secretory
procesess

1) The immune system is integrated by a highly complex

regulated group of cells.
2) that may interact in a cellcell manner and may also
respond to intercellular messages.
3) The immune response can be modified by
a) Diet
b) pharmacological agents
c) environmental pollutants
d) and naturally occurring food chemicals such as
vitamins and flavonoids.

4) Some flavonoids display a remarkable array of

biochemical and pharmacological actions.
5) that affect the function of immune and inflammatory cells
such as
a) T cells,
b) B cells,
c) macrophages,
d) neutrophils,
e) mast cells, or basophils.

6) Several flavonoids specifically affect enzyme systems critically

involved in the generation of inflammatory processes.
7) especially tyrosine and serine-threonine protein kinases.
8) These enzymes are involved in signaling transduction and cell
activation processes such as

a) T cell proliferation,
b) B lymphocyte activation or
c) cytokine production by stimulated monocytes

Modulation of proinflammatory
enzyme activities
ACTIVITY

Modulation of
proinflammatory
enzyme activities

MECHANISM

inhibition of
Arachidonic
acid enzyme

inhibition of
NO synthase

EFFECT

Inflammatory
mediators:
NO, Leukotrienes,
prostaglandins

1) Many investigations have shown that different flavonoid

molecules modulate the activity of arachidonic acid
metabolizing enzymes such as
a) phospholipase ,
b) cyclooxygenase (COX) and lipoxygenase (LOX)
c) And the nitric oxide (NO) producing enzyme,
nitric oxide synthase (NOS).
2) The inhibition of these enzymes reduces the production of
AA, prostaglandins, leucotrienes, and NO. which are
mediators of inflammation.
3) Thus, the inhibition of these enzymes by flavonoids may be
one of the most important mechanisms of their antiinflammatory activity.

Modulation of the production of

other proinflammatory molecules
ACTIVITY

Modulation of the
production of other
proinflammatory
molecules

MECHANISM

Modulation
of cytokine
production

EFFECT

Inflammatory
Cytokine:
TNF- ,
Interleukines.

1) In addition to COX-2 several cytokines are deeply

associated with inflammatory diseases
2) In particular, tumor necrosis factor-a (TNF-a) is prominent
contributors to chronic inflammatory responses.
3) The comparison of molecular structures from different
flavonoids shows that
a) That the presence of a double bond at position C2
C3 of the C ring
b) With oxo function at position 4,
c) Along with the presence of OH groups at positions
30 and 40 of the B ring
are required for optimal inhibition of LPS
stimulated TNF-a release.

Modulation of proinflammatory
gene expression
ACTIVITY

Modulation of
proinflammatory
gene expression

MECHANISM

Modulation
of single
transduction

EFFECT

proinflammatory
Gene transcription

1) In recent years, several lines of evidence have supported

the idea that certain flavonoids are modulators of
proinflammatory gene expression
2) thus leading to the attenuation of the inflammatory
response
3) It is not known to what extent these proinflammatory gene
expression changes contribute to the inflammatory
response
4) but is evident that flavonoids show anti-inflammatory
activity, at least in part, by affecting mRNA levels.

5) The mechanisms by which flavonoids block

proinflammatory gene expression are
currently being investigated
6) but pioneer studies suggest an effect on
transcriptional activity suppression in
response to inflammatory stimuli.

CONCLUSIONS
Excessive inflammation is considered as a critical
factor in many human diseases, including two
of the most extended burdens in the world:
cancer and cardiovascular diseases.
Epidemiological studies have demonstrated an
inverse relationship between dietary flavonoid
intake and prevalence and risk of these
diseases.
So that, flavonoids research have received much
attention over the past years.

References
Flavonoids
as
anti-inflammatory
agents:
implications in cancer and cardiovascular disease
Ana Garca-Lafuente ,Eva Guillamon.
Ana Villares,Mauricio A. Rostagno.
Jose Alfredo Martnez.

The Effects of Plant Flavonoids on Mammalian Cells:

Implications for Inflammation, Heart Disease, and
Cancer
ELLIOTT MIDDLETON, JR., CHITHAN KANDASWAMI
AND THEOHARIS C. THEOHARIDES1

References
Organic Chemistry of Natural products Vol
2- Gurdeep.R.Chatwal
Organic Chemistry- Reactions and ReagentsO.P Aggarwal
Chemistry of Natural Products- SV Bhat, BH
Nagasampagi, M.Sivakumar